P871: IDECABTAGENE VICLEUCEL (IDE-CEL) IN PATIENTS WITH AN INADEQUATE RESPONSE TO FRONTLINE AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT): RESULTS FROM KARMMA-2 COHORT 2C
Authors: Melissa Alsina, Madhav Dhodapkar, Jesus Berdeja, Krina Patel, Shambavi Richard, Ravi Vij, Xavier Leleu, Daniel Egan, P. Leif Bergsagel, Reshef Ran, Saad Z Usmani, Anna Truppel-Hartmann, Debashree Basudhar, Ethan Thompson, Xirong Zheng, Xiaobo Zhong, Chiara Greggio, Mihaela Popa Mckiver, Marlene Carrasco Alfonso, David Siegel
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Patients (pts) with multiple myeloma (MM) without a deep response post-ASCT have a higher risk of progression/death. Ide-cel led to frequent, deep, and durable responses in triple-class–exposed (TCE) relapsed and refractory MM (RRMM) in the fourth line and beyond (4L+) setting in KarMMa, and significantly improved median progression-free survival (PFS) and overall response rate (ORR) vs standard regimens in 3–5L TCE RRMM in KarMMa-3. KarMMa-2 (NCT03601078) is a multicohort phase 2 trial of ide-cel in clinical high-risk MM. Pts in cohort 2c had inadequate response after frontline ASCT (< very good partial response [VGPR]). Aims: To evaluate the efficacy and safety of ide-cel in cohort 2c. Methods: Eligible pts had newly diagnosed MM (NDMM), received ≥3 cycles of induction therapy (tx; including a proteasome inhibitor, immunomodulatory agent, and dexamethasone), achieved <VGPR 70–110 d after ASCT (single/tandem), and had an ECOG PS ≤1. After lymphodepletion, pts received a single infusion of ide-cel at planned dose range 150–450×106 CAR+ T cells. At investigator discretion, pts could receive maintenance tx post-infusion. Primary endpoint was complete response (CR) rate (by investigator per IMWG criteria). Secondary endpoints included ORR, VGPR rate, time to response (TTR), duration of response, PFS, overall survival, safety, and pharmacokinetics; soluble BCMA (sBCMA) level and minimal residual disease negativity (MRD−; sensitivity <10-5) were exploratory endpoints. Results: Ide-cel was infused in 31/32 enrolled pts. Median age was 64 y, 67.7% of pts had ECOG PS 0, and 41.9% had R-ISS stage I disease (none had stage III); 87.1% had a best response of partial response to ASCT. High-risk cytogenetics were seen in 9.7% of pts; 3.2% had high tumor burden and 6.5% had extramedullary disease. At data cutoff (Mar 14, 2022; median follow-up, 27.9 mo), ORR was 87.1% and CR rate was 74.2% (Table); median TTR was 1 (range, 0.9–2.8) mo. Grade (G) 3/4 adverse events (AEs) occurred in 29 (93.5%) pts, most commonly neutropenia (80.6%), leukopenia (29.0%), and anemia (22.6%); none were G5. G1/2 cytokine release syndrome (CRS) occurred in 18 (58.1%) pts; no pts had ≥G3. Two (6.5%) pts had investigator-identified neurotoxicity (iiNT); 1 G1 and 1 G3. Induction of inflammatory cytokines was observed with median fold change from baseline (BL) to peak levels (Cmax) of 2.68 for IFN-γ, 4.31 for IL-6, 6.19 for IL-8, and 5.07 for IL-10. However, median fold change from BL to Cmax was lower than that in 4L+ RRMM in KarMMa (P<0.001), except for IL-8 (P=0.556). Robust cell expansion was seen in all pts (Table) despite low tumor burden, as indicated by sBCMA level at infusion (range, 6.5–154.0 ng/mL; n=30); cellular expansion was higher in pts with ≥CR vs <CR. sBCMA was cleared ≤2 mo post-infusion in 24/31 (77.4%) pts; including 22 with ≥CR. In evaluable pts with ≥CR, 16/23 (69.6%; 95% CI, 49.1–84.4) had MRD− at 6 and 12 mo post-infusion. Of these, 11 had MRD− at 24 mo; 5 had no/indeterminate data. In all pts, 17/28 (60.7%; 95% CI, 42.4–76.4) had MRD− at 12 mo. Summary/Conclusion: Ide-cel showed frequent, deep, and durable responses in pts with <VGPR to frontline ASCT, with an early, deep clearance of tumor in pts with ≥CR that was sustained at 2 y. Lower incidence of CRS/iiNT and lower levels of inflammatory cytokines were seen in NDMM vs 4L+ RRMM. These results support a favorable clinical benefit–risk profile of ide-cel in NDMM.Keywords: CAR-T, Multiple myeloma, Minimal residual disease (MRD), High risk